ArticleEuropean journal of cancer (Oxford, England : 1990)2010
Amplification of thymidylate synthetase in metastatic colorectal cancer patients pretreated with 5-fluorouracil-based chemotherapy.
Article in European journal of cancer (Oxford, England : 1990), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Plasma deoxyuridine as a surrogate marker for toxicity and early clinical response in patients with metastatic colorectal cancer after 5-FU-based therapy in combination with arfolitixorin.Cancer chemotherapy and pharmacology · 2021Trial
- Multi-Omics Analysis of TYMS as a Prognostic Biomarker and Therapeutic Target for Lung Adenocarcinoma.Cancer medicine · 2026Article
- Copy number alteration fingerprint predicts the clinical response of oxaliplatin-based chemotherapy in metastatic colorectal cancer.NPJ precision oncology · 2026Article
- Article
- Article
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients?International journal of molecular sciences · 2022Review
- Novel Diagnostic and Therapeutic Options forFrontiers in pharmacology · 2022Article
- Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.Clinical and translational medicine · 2021Article
- Review
- Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of micro-ribonucleic acids.World journal of gastrointestinal oncology · 2020Review
- YES1 amplification confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive cancer.British journal of cancer · 2020Article
- 5-Fluorouracil treatment induces characteristic T>G mutations in human cancer.Nature communications · 2019Article
- Identification of important invasion and proliferation related genes in adrenocortical carcinoma.Medical oncology (Northwood, London, England) · 2019Article
- Biomarkers in colorectal cancer: Current clinical utility and future perspectives.World journal of clinical cases · 2018Review
- Evaluation of effects of thymidylate synthase and excision repair cross-complementing 1 polymorphisms on chemotherapy outcome in patients with gastrointestinal tumors using peripheral venous blood.Oncology letters · 2016Article
- Clinical observation of gene expression-guided chemoradiation therapy for nonsurgical esophageal squamous cell carcinoma patients: a retrospective analysis of 36 cases.OncoTargets and therapy · 2016Article
- Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp.Cancer cell international · 2015Article
- MicroRNAs as novel predictive biomarkers and therapeutic targets in colorectal cancer.World journal of gastroenterology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Resistance to 5-fluorouracil (5-FU) represents a major contributor to cancer-related mortality in advanced colorectal cancer patients. Genetic variations and expression alterations in genes involved in 5-FU metabolism and effect have been shown to modulate 5-FU sensitivity in vitro, however these alterations do not fully explain clinical resistance to 5-FU-based chemotherapy. To determine if alterations of DNA copy number in genes involved in 5-FU metabolism-impacted clinical resistance to 5-FU-based chemotherapy, we assessed thymidylate synthetase (TYMS) and thymidine phosphorylase (TYMP) copy number in colorectal liver metastases. DNA copy number of TYMS and TYMP was evaluated using real time quantitative PCR in frozen colorectal liver metastases procured from 62 patients who were pretreated with 5-FU-based chemotherapy prior to surgical resection (5-FU exposed) and from 51 patients who received no pretreatment (unexposed). Gain of TYMS DNA copy number was observed in 18% of the 5-FU exposed metastases, while only 4% of the unexposed metastases exhibited TYMS copy gain (p = 0.036). No significant differences were noted in TYMP copy number alterations between 5-FU-exposed and -unexposed metastases. Median survival time was similar in 5-FU-exposed patients with metastases containing TYMS amplification and those with no amplification. However, TYMS amplification was associated with shorter median survival in patients receiving post-resection chemotherapy (hazard ratio = 2.7, 95% confidence interval = 1.1-6.6; p = 0.027). These results suggest amplification of TYMS amplification as a putative mechanism for clinical resistance to 5-FU-based chemotherapy and may have important ramifications for the post-resection chemotherapy choices for metastatic colorectal cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.